1. Field of the Invention
The invention generally relates to use of a suspension culture of cells followed by a period of culture under a hydrostatic load to promote chondrogenesis or osteogenesis without the use of a scaffold or foreign matrix.
2. Related Art
Osteoarthritis is a debilitating joint disease that causes pain and dysfunction. It is characterized by the degeneration of articular cartilage, and affects over 20 million people nationwide. Clinical and research studies are currently striving to understand the disease progression of osteoarthritis and develop improved methods of treatment. Attempts are being made to repair, regenerate, replace, and relieve the pain caused by osteoarthritis.
Exemplary methods of treatment for osteoarthritis currently considered are osteochondral transplantation, microfracture surgery, and tissue engineering. Osteochondral transplantation consists of removing a healthy full depth bone plug from an area that experiences low loads and subsequently press fitting the plug into a hole cut in the damaged location. Although osteochondral transplantation endures over the short-tem, the long-term performance of this technique has not yet been observed. For example, it has not yet been determined if moving tissue from a low-weight bearing area to a high-weight bearing location will ultimately lead to degeneration resulting from mechanical overloading.
In microfracture surgery, several small holes in the range of about 0.5 mm to about 1.0 mm in diameter are drilled into the subchondral bone beneath an area of damaged articular cartilage. Subsequently, blood and bone marrow (which contains stem cells) seep out into the drilled holes creating a blood clot that ultimately produces a material called fibrous cartilage. Although this technique has been used in young patients and athletes and has resulted in pain relief in about 75% of patients and improved joint functionality, the procedure has several limitations. For example, the procedure is less effective in older and overweight patients and the long-term results of the repair have not been characterized.
Alternatively, repair tissue that has mechanical and biological characteristics similar to native cartilage may be engineered and surgically implanted into a patient. Here, cells such as chondrocytes, may be cultured and used to replace the damaged region of cartilage within the patient with a healthy, phenotypically similar material. There are a multitude of choices of scaffolds, cells, signaling molecules, and culture techniques, which may be considered, each of which may present unique complicated biological and biomechanical design problems. Moreover, there are many disadvantages associated with the use of frequently used scaffold matrix materials that include collagen, fibrin, alginate, agarose, and hyluronan such as bio-incompatibility, the presence of foreign body cell-reactions, and biodegradability. Additionally, chondrocytes grown in these ways for even short periods of time begin to de-differentiate and eventually take on a fibroblastic phenotype.
It can be seen from the foregoing discussion that existing techniques for treatment of osteoarthritis have many limitations associated with them such as lack of characterization of the long-term effects, bio-incompatibility, and biological and biomechanical design issues. Thus, there is a need for improved methodologies to engineer repair tissue that has mechanical and biological characteristics similar to native cartilage.